Purpose: Clinicobiological characteristics of neuroblastic tumor (NT) expressing c-kit tyrosine kinase receptor and/or its ligand, stem cell factor (SCF), are debated. This study aimed at investigating the clinicobiological features of primary NTs expressing c-kit and/or SCF in order to define the clinical relevance of selective therapeutic targeting. Experimental Design: c-Kit and SCF expression was studied in 168 NTs using immunohistochemistry and in 106 of 168 using Northern blot. Quantitative determination of c-kit expression in 54 additional NTs was also done using real-time reverse transcription-PCR. Correlations between c-kit and SCF expression and clinicobiological features were analyzed Using chi(2) test, univariate, and multivariate regression analyses. Results: c-Kit protein was detected in 21 of 168 NTs (13%) and its mRNA in 23 of 106 NTs (22%). SCF protein was shown in 30 of 106 NTs (28%) and its mRNA in 33 of 106 NTs (31%). No mutations in exon 11 of e-kit gene were identified. By univariate analysis, c-kit and SCF expression correlated with advanced stage, MYCN amplification, and 1p36 allelic loss. Cox simple regression analysis showed that overall survival probability was 17% in the c-kit-positive subset versus 68% in the negative (P<0.001), 43% in the SCF-positive subset versus 78% in the negative (P<0.001). When using real-time reverse transcription-PCR, significant levels of c-kit mRNA were found in 35 of 54 NTs (65%), but the correlations with clinicobiological features were no longer documented. Conclusions: c-Kit expression can be detected in the majority of primary NTs. High levels of expression are preferentially found in tumors with unfavorable clinicobiological variables. c-Kit may represent a useful therapeutic target in a subset of otherwise untreatable NTs.

Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumors / Uccini, Stefania; O., Mannarino; H. P., Mcdowell; U., Pauser; R., Vitali; P. G., Natali; P., Altavista; T., Andreano; S., Coco; R., Boldrini; Bosco, Sandro; Clerico, Anna; Cozzi, Denis; A., Donfrancesco; A., Inserra; G., Kokai; P. D., Lotsy; M. R., Nicotra; G., Raschella'; G. P., Tonini; Dominici, Carlo. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 11:1(2005), pp. 380-389.

Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumors

UCCINI, Stefania;BOSCO, Sandro;CLERICO, Anna;COZZI, Denis;DOMINICI, Carlo
2005

Abstract

Purpose: Clinicobiological characteristics of neuroblastic tumor (NT) expressing c-kit tyrosine kinase receptor and/or its ligand, stem cell factor (SCF), are debated. This study aimed at investigating the clinicobiological features of primary NTs expressing c-kit and/or SCF in order to define the clinical relevance of selective therapeutic targeting. Experimental Design: c-Kit and SCF expression was studied in 168 NTs using immunohistochemistry and in 106 of 168 using Northern blot. Quantitative determination of c-kit expression in 54 additional NTs was also done using real-time reverse transcription-PCR. Correlations between c-kit and SCF expression and clinicobiological features were analyzed Using chi(2) test, univariate, and multivariate regression analyses. Results: c-Kit protein was detected in 21 of 168 NTs (13%) and its mRNA in 23 of 106 NTs (22%). SCF protein was shown in 30 of 106 NTs (28%) and its mRNA in 33 of 106 NTs (31%). No mutations in exon 11 of e-kit gene were identified. By univariate analysis, c-kit and SCF expression correlated with advanced stage, MYCN amplification, and 1p36 allelic loss. Cox simple regression analysis showed that overall survival probability was 17% in the c-kit-positive subset versus 68% in the negative (P<0.001), 43% in the SCF-positive subset versus 78% in the negative (P<0.001). When using real-time reverse transcription-PCR, significant levels of c-kit mRNA were found in 35 of 54 NTs (65%), but the correlations with clinicobiological features were no longer documented. Conclusions: c-Kit expression can be detected in the majority of primary NTs. High levels of expression are preferentially found in tumors with unfavorable clinicobiological variables. c-Kit may represent a useful therapeutic target in a subset of otherwise untreatable NTs.
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Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumors / Uccini, Stefania; O., Mannarino; H. P., Mcdowell; U., Pauser; R., Vitali; P. G., Natali; P., Altavista; T., Andreano; S., Coco; R., Boldrini; Bosco, Sandro; Clerico, Anna; Cozzi, Denis; A., Donfrancesco; A., Inserra; G., Kokai; P. D., Lotsy; M. R., Nicotra; G., Raschella'; G. P., Tonini; Dominici, Carlo. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 11:1(2005), pp. 380-389.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/236989
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